Varicells Zoster Virus (VZV) causes widespread disease in both adults (usually shingles) and in children (usually chicken pox). In immunocompromised individuals it is one of the most prevalent virus infections, is very painful and often fatal. Little is known of the molecular biology of VZV and of basic properties such as the structure and synthesis of its DNA. This proposal aims to investigate the size, configuration, internal organization and biological activity of VZV DNA by the following means. The kinetic complexity of VZV DNA will be determined by liquid-liquid hybridization studies. Partial denaturation maps of intact VZV DNA as well as cloned VZV DNA fragments will be generated and correlated with restriction enzyme studies. The size, genetic origin and biological activity of supercoiled VZV DNA molecules will be analyzed. The extent and location of observed sequence differences among DNAs from a variety of VZV strains will be determined by restriction enzyme analysis, and analysis of heteroduplexes by S1 nuclease digestion and electron microscopy. Our observation of strain differences in VZV isolates visible as alterations in restriction patterns of their DNAs will allow a detailed survey of both varicella and zoster infections both from an epidemiological standpoint and as an analysis of lesion development and regression. Finally, in order to gain an understanding of the life cycle of this virus in its human host, in situ nucleic acid hybridization is proposed with VZV DNA using thin sections of frozen and/or explanted dorsal root ganglia. These studies should allow determination of the location and extent of VZV DNA present in ganglia. Techniques to be employed include liquid-liquid hybridization, partial denaturation, restriction enzyme analysis, nick-translation, gel electrophorasis, blotting, DNA transfection, heteroduplex mapping, in situ hybridization and the use of cloned DNA fragments.